The expression profile and bioinformatics analysis of microRNAs in human bronchial epithelial cells treated by beryllium sulfate

• Published in: Journal of applied toxicology Vol. 41; no. 8; pp. 1275 - 1285
• Main Authors: Yi, Shan, Liu, Yan‐ping, Li, Xun‐ya, Yuan, Xiao‐yan, Wang, Ye, Cai, Ying, Lei, Yuan‐di, Huang, Lian, Zhang, Zhao‐hui
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2021
• Subjects: 16HBE cell; Beryllium; Beryllium - toxicity; Beryllium compounds; beryllium sulfate; Bioinformatics; Blotting, Western; Bronchi - cytology; Bronchi - drug effects; Bronchi - metabolism; Cell Line; Cell Survival - drug effects; cytokine; Cytokines; Cytokines - metabolism; Encyclopedias; Enzyme-Linked Immunosorbent Assay; Epithelial cells; Epithelium; Gene expression; Gene regulation; Genes; Genomes; High-Throughput Nucleotide Sequencing; Humans; Inflammation; Interferon; Interleukins; Lung diseases; MAP kinase; MicroRNAs; MicroRNAs - metabolism; miRNA; miRNAs; Nitric oxide; Nitric-oxide synthase; Polymerase chain reaction; Prostaglandin endoperoxide synthase; Real-Time Polymerase Chain Reaction; Respiratory Mucosa - cytology; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Signal transduction; Sulfates; Toxicants; Toxicity; Transcription; Transcriptome - drug effects; Tumor necrosis factor; Tumor necrosis factor-TNF; Vascular endothelial growth factor; cytokine; 16HBE cell; miRNAs; beryllium sulfate; bioinformatics
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4116

Beryllium and its compounds are systemic toxicants that mainly accumulate in the lungs. As a regulator of gene expression, microRNAs (miRNAs) were involved in some lung diseases. This study aimed to analyze the levels of some inflammatory cytokine and the differential expressions of miRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) and to further explore the biological functions of differentially expressed miRNAs. The profile of miRNAs in 16HBE cells was detected using the high‐throughput sequencing between the control groups (n = 3) and the 150 μmol/L of BeSO4‐treated groups (n = 3). Bioinformatics analysis of differentially expressed miRNAs was performed, including the prediction of target genes, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was applied to verify some damage‐related miRNAs. We found that BeSO4 can increase the levels of some inflammatory cytokine such as interleukin‐10 (IL‐10), tumor necrosis factor‐alpha (TNF‐α), interferon‐γ (IFN‐γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2). And BeSO4 altered miRNAs expression of 16HBE cells and a total of 179 differentially expressed miRNAs were identified, including 88 upregulated miRNAs and 91 downregulated miRNAs. The target genes predicted by 28 dysregulated miRNAs were mainly involved in the transcription regulation, signal transduction, MAPK, and VEGF signaling pathway. The qRT‐PCR verification results were consistent with the sequencing results. miRNA expression profiling in 16HBE cells exposed to BeSO4 provides new insights into the toxicity mechanism of beryllium exposure. Beryllium and its compounds are systemic toxicants that mainly accumulate in the lungs. As a regulator of gene expression, microRNAs (miRNAs) were involved in some lung diseases. This study aimed to analyze the levels of some inflammatory cytokine and the differential expressions of miRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) and further explore the biological functions of differentially expressed miRNAs. We found that BeSO4 can increase the levels of some inflammatory cytokine such as interleukin‐10 (IL‐10), tumor necrosis factor‐alpha (TNF‐α), interferon‐γ (IFN‐γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2). And BeSO4 altered miRNAs expression of 16HBE cells and a total of 179 differentially expressed miRNAs were identified, including 88 up‐regulated miRNAs and 91 down‐regulated miRNAs. The target genes predicted by 28 dysregulated miRNAs were mainly involved in the transcription regulation, signal transduction, MAPK, and VEGF signaling pathway. miRNA expression profiling in 16HBE cells exposed to BeSO4 provides new insights into the toxicity mechanism of beryllium exposure.